Mucosal Tissue Dressing And Method Of Use

ABSTRACT

A method and apparatus for reducing or eliminating pain after surgical procedures related to mucosal tissue, including tonsillectomy, adenoidectomy, or other pharyngeal operations. Certain embodiments provide a biodegradable film or covering that serves as a mechanical barrier to reduce pain caused, for example, by friction between solid food and healing tissue in the first few days after surgery. Some embodiments may include one or more therapeutic substances for locally reducing pain, facilitating healing and/or otherwise treating mucosal tissue at or near a tonsil bed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/017,976, filed Dec. 31, 2007, and U.S. Provisional Application No.61/052,413, filed May 12, 2008, both of which are herein incorporated byreference in its entirety.

BACKGROUND OF THE INVENTION

Tonsillectomy and adenoidectomy are two of the most common surgicalprocedures performed on children. Both tonsillectomy and adenoidectomyare associated with considerable post-operative pain that may often lastas long as two weeks. Due to this post-operative pain, which is mostsevere when trying to swallow food, children typically cannot eat solidfood for at least two days after surgery and often for as long as sixdays after surgery. In addition to post-operative pain, children alsocommonly suffer from post-operative bleeding, nausea, and/or bad breathafter tonsillectomy/adenoidectomy. Although tonsillectomy andadenoidectomy are performed less commonly on adults, the procedurescause similar post-surgical pain and discomfort in adult patients.

Generally, surgical procedures on mucosal tissue, such as tonsillectomyand adenoidectomy, present several post-operative challenges. Mucosaltissue is typically very delicate and difficult to bandage. Mucosaltissue often must stay wet to heal and to perform its intended function.Damaged mucosal tissue can produce significant patient discomfort.

A number of tonsillectomy/adenoidectomy procedures have been developedin an attempt to reduce the post-operative pain and discomfort caused bythe procedure. For example, the Coblation Tonsillectomy proceduredeveloped by Arthrocare Corporation (Austin, Tex.) was developed as a“less invasive,” and thus less painful, tonsillectomy method. However,even using the Coblation Tonsillectomy procedure or other less invasiveprocedures, post-operative pain and bleeding are still significant formany children and adult patients, often preventing them from eating foodfor days after their surgeries. To date, no satisfactory post-operativetreatments have been developed to alleviate this pain and to allowpatients to comfortably eat after tonsillectomy and adenoidectomyprocedures.

Therefore, a need exists for a post-surgical treatment that would helpchildren and adult patients recover from tonsillectomy andadenoidectomy. Ideally, such a treatment would act as a barrier toprotect mucosal tissue at and around the surgical site to make it easierand less painful for a patient to swallow. Ideally, the barrier wouldadhere to mucosal tissue even with the abrasive forces of swallowingand, in addition to reducing pain, would also reduce bleeding. At leastsome of these objectives will be met by various embodiments of thepresent invention.

In addition to post-tonsillectomy/adenoidectomy treatment, there aremany other treatments in the ear, nose, throat or mouth that could beperformed or enhanced with a mucosal tissue dressing. For example, itwould be desirable to have a mucosal tissue dressing that could adhereto tissue and deliver one or more therapeutic substances to a desiredarea in the ear, nose, throat or mouth. It would also be beneficial tohave a dressing for stopping a cerebrospinal fluid leak, reducing bloodloss from an incision, acting as a bolster or support to a piece oftissue and/or the like. In any of these contexts, the challenges ofproviding a mucosal tissue dressing are similar, in that the dressingmust stay in place long enough, perform its function, and not interferewith normal physiological function. Various embodiments of the presentinvention will also meet at least some of these objectives for purposesother than a post-tonsillectomy/adenoidectomy dressing.

BRIEF SUMMARY OF THE INVENTION

Certain embodiments of the present invention provide a method forreducing or eliminating pain after surgical procedures related tomucosal tissue, including tonsillectomy, adenoidectomy, or otherpharyngeal operations.

Certain embodiments of the present invention provide a biodegradablefilm or covering that serves as a mechanical barrier to reduce paincaused, for example, by friction between solid food and healing tissuein the first few days after surgery.

Some embodiments may include one or more therapeutic substances forlocally reducing pain, facilitating healing and/or otherwise treatingmucosal tissue at or near a tonsil bed. In some embodiments, multiplelayers of tissue dressing may contain different therapeutic substances.Some embodiments may allow a physician to inject or otherwise apply oneor more therapeutic substances to a tissue dressing before applying thedressing to the patient.

In some embodiments, a tissue dressing may be applied to areas otherthan a tonsil bed and for purposes other than easing post-tonsillectomypain and discomfort. For example, in some embodiments, a tissue dressingmay be applied to a nasal septum to facilitate or enhance a nasalseptoplasty procedure. In various embodiments, a tissue dressing may beapplied at any of a number of locations in a nasal or paranasal cavity,in paranasal sinuses, in polyps located in the nasal or paranasalcavity, in a Eustachian tube, in a mouth or the like, for performing anynumber of functions. For example, the tissue dressing may be placed as atherapeutic drug delivery vehicle. In some embodiments, the tissuedressing may be used to stiffen or fortify soft tissues, such as fortreating sleep apnea. In other embodiments, the tissue dressing may beused to cover or plug up cerebrospinal fluid (CSF) leaks. In still otherembodiments, a tissue dressing may be used as an iontophoresis padthrough which electrical energy may be passed. These and otherembodiments are described further below with reference to the attacheddrawings.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 illustrates a perspective view of a dressing, according to oneembodiment of the present invention.

FIG. 2 illustrates a perspective view of a two layer dressing, accordingto one embodiment of the present invention.

FIG. 3 illustrates a perspective view of a multilayer layer dressing,according to one embodiment of the present invention.

FIG. 4 illustrates a perspective view of a tissue dressing having analternative shape, according to one embodiment of the present invention.

FIG. 5 illustrates a perspective view of a cylinder-shaped tissuedressing, such as for use in or near a Eustachian tube, according to oneembodiment of the present invention.

FIG. 6 illustrates a method of preparing a dressing for use, accordingto one embodiment of the present invention.

FIG. 7 illustrates a method of packaging and preparing a multi-layerdressing for use, according to one embodiment of the present invention.

FIGS. 8A and 8B illustrate methods of packaging a dressing for use,according to alternative embodiments of the present invention.

FIG. 9 illustrates a method of packaging a dressing for use, accordingto an alternative embodiment of the present invention.

FIG. 10 illustrates a device and method useful in applying an in-situdressing, according to one embodiment of the present invention.

FIG. 11A illustrates a device and method useful in applying an in-situdressing and FIG. 11B illustrates a close-up view of a section of thesame device and method, according to one embodiment of the presentinvention.

FIG. 12 illustrates a method for applying a tonsillectomy dressingaccording to one embodiment of the present invention.

FIG. 13 illustrates a method for applying an in-situ tonsillectomydressing according to one embodiment of the present invention.

FIG. 14 illustrates a method for applying a film to a nasal septum,according to one embodiment of the present invention.

FIG. 15 illustrates a method for applying a tissue dressing to aposterior aspect of a tongue in performing a sleep apnea treatmentprocedure, according to one embodiment of the present invention.

FIG. 16 illustrates a lift-off adhesion test method.

FIG. 17 illustrates a peel-off adhesion test method.

DETAILED DESCRIPTION OF THE INVENTION

Various embodiments of the present invention generally comprise amucosal tissue dressing for applying to mucosal tissue. In some cases,the tissue dressing may be applied after a surgical excision of tissue,such as in a tonsillectomy or adenoidectomy procedure, while in othercases it may be applied to tissue that has not been operated upon. Invarious embodiments, the dressing may have any of a number of suitableconfigurations, some of which are described further below. The dressingmay also include one or more therapeutic substances, which it maydeliver to tissue to which it is applied and/or to surrounding tissues.

Certain embodiments of the present invention are useful for reducingpost-operative pain associated with surgery performed on or near mucosaltissue. It may be desirable for dressings made and used according tocertain embodiments of the present invention to carry out some or all ofthe following functions and have some or all of the following desirableproperties:

-   -   The dressing can be applied intraoperatively, quickly and        easily, immediately after completion of surgery at the site.    -   The dressing can be readily adapted for use following a medical        or surgical procedure, such as tonsillectomy or adenoidectomy.    -   The dressing forms a mechanical barrier that is sufficient to        shield the healing tissue from abrasion, such as that due to        swallowing of solid food.    -   The dressing has some flexibility in both dry and wet        conditions. The dressing conforms easily to complex shapes.    -   The dressing includes a hydrated film that does not swell        excessively and is both elastic and flexible after adhesion to        tissue.    -   The dressing includes a film that sets and/or adheres rapidly to        moist tissue and is firm and not tacky when set.    -   The dressing adheres to the surgical bed for 12 hours to 5 days.    -   The dressing stays intact and in place for a minimum of 48        hours.    -   The dressing is completely dissolved by 10-14 days.    -   The dressing does not swell to create an obstruction or become        uncomfortable.    -   The dressing begins to dissolve slowly with no risk of release        of large material fragments that cause a choking hazard or other        complication.    -   The dressing does not delay healing and in some embodiments may        facilitate healing.    -   In oral applications, the dressing does not taste bad. In some        applications, the dressing may even be flavored.    -   The dressing provides a “cool” sensation.    -   The dressing is made of inexpensive materials.

Embodiments of the present invention disclosed herein may contain someor all of these properties and perform some or all of these functions.

Certain embodiments of the present invention are applied to a surgicalbed like a bandage or a dressing. The dressing can be preshaped and/orcut to a custom size and shape. The bandage embodiments can have aremovable backing, which reveals an adhesive layer when removed. Thedressing may provide a platform useful for drug delivery or the releaseof other therapeutic substances.

Generally, a mucosal tissue dressing may perform adhesive, barrier,mechanical and/or dissolving functions in various embodiments. In manyembodiments, a tissue dressing may perform a local function, such asreduction of pain and discomfort, reduction of bleeding, reduction ofCSF leakage and/or the like. In some embodiments, a tissue dressing mayalternatively or additionally also perform a central function, such asdelivering a drug to the blood stream or central nervous system. Invarious embodiments, the tissue dressing may provide a platform for drugdelivery for a variety of respiratory and/or ear, nose and throat(“ENT”) diseases or conditions and may be applied to any mucosalsurface. In one embodiment, for example, a tissue dressing may be usedas an adhesion barrier within the nasal cavity or sinuses to preventiatrogenic fusing of tissue after surgery. In another example, thetissue dressing may be applied to surfaces that are the site ofrecurrent polyps to provide a barrier to recurrence either mechanicallyor through sustained drug delivery.

FIG. 1 illustrates a perspective view of one embodiment of the presentinvention. Dressing 100 has an adhesive surface 110 and a barriersurface 120. Adhesive surface 110 is designed to contact and adhere totissue, such as mucosal tissue or mucous membranes. Adhesive surface 110can be textured to facilitate adhesion to tissue. Adhesive surface 110can have textures such as fibrous, porous, dimpled, striated or othertextures, including combinations thereof. Adhesive surface textures mayalso be selected to facilitate healing and to facilitate removal ofdressing 100 in certain embodiments where removal is part of the methodof treatment.

Referring still to FIG. 1, barrier surface 120 is designed to provideresistance to mechanical forces, such as abrasion. Barrier surface 120can also provide resistance to infiltration or diffusion of substancesfrom the biological milieu surrounding the site where the dressing isapplied. Barrier surface 120 may be lubricious to prevent adhesion offoreign particles such as food. Barrier surface 120 can have textures,such as those described for adhesive surface 110 or others. Barriersurface textures may be selected to discourage adhesion of materials todressing 100. Both the barrier surface texture and the adhesive surfacetexture may be selected to facilitate dissolution of dressing 100 incertain embodiments where dissolution is part of the method oftreatment.

FIG. 2 illustrates a perspective view of one embodiment of the presentinvention. Dressing 200 has an adhesive layer 210 and a barrier layer220. Adhesive layer 210 can be structured to promote tissue adhesion.For example, adhesive layer 210 may have a porous structure thatfacilitates penetration of tissue into the layer. Generally, highsurface area contact between two surfaces promotes adhesion. Anystructure that increases the surface area contact between the surgicalbed and adhesive layer 210 may be useful.

Referring again to FIG. 2, adhesive layer 210 can be structured totailor its dissolution rate. Some materials, such as polyanhydrides,dissolve from their surface. Other materials, such as poly(a-hydroxyesters), dissolve from their bulk. For both surface-eroding andbulk-eroding materials, control of the surface area can have an impacton the dissolution rate. A preferred structure for adhesive layer 210can balance the surface area requirements for adhesiveness with thosefor dissolution. Also, as described in more detail below, surface areacan have an effect on the drug delivery profile of the dressing. Apreferred structure for adhesive layer 210 can take the drug deliveryeffects into account as well.

Still referring to FIG. 2, adhesive layer 210 includes an adhesivesurface 215, which is designed to contact and adhere to tissue. Adhesivesurface 215 may be textured as described above in reference to FIG. 1.

Again referring to FIG. 2, barrier layer 220 may be structured topromote mechanical durability and resistance to infiltration. Recallingthat dressings of certain embodiments of the present invention may beflexible, barrier layer 220 may have a structure that providesflexibility and durability, to allow for natural tissue movement duringswallowing without damage from the passage of solid food. As withadhesive layer 210, barrier layer can be structured to tailor itsdissolution rate. Barrier layer 220 may be made from a surface-erodingor a bulk eroding material, or a combination thereof. Thus, a preferredstructure for barrier layer 220 can balance the structural requirementsfor mechanical durability with those for dissolution. Since barrierlayer 220 can also act as a reservoir for drug delivery, a preferredstructure for barrier layer 220 can take the drug delivery effects intoaccount as well.

Still referring to FIG. 2, barrier layer 220 includes a barrier surface225, which is designed to provide resistance to penetration bymechanical forces, foreign particles or bacteria and infiltration ofsurrounding tissue components. Barrier layer 220 and/or barrier surface225 can provide shock absorbing properties. Barrier surface 225 may betextured as described above in reference to FIG. 1.

The total thickness of the dressing can be in a range from about 0.1 mmto about 0.7 mm. The preferred thickness of certain embodiments is about0.3 mm. The adhesive layer thickness can be about 0.1 mm and the barrierfilm thickness can be about 0.2 mm. In certain embodiments, thethickness of the dressing may not be uniform. For example, in certainembodiments, the edges of the dressing may be thinner than the center ofthe dressing.

FIG. 3 illustrates a perspective view of one embodiment of the presentinvention. Dressing 300 is composed of adhesive layer 310 and barrierlayer 330. Connecting layer 320 connects adhesive layer 310 and barrierlayer 330. Connecting layer 320 can be structured as previouslydescribed with regard to adhesive layers and barrier layers. That is,connecting layer 320 can have a structure that is tailored to produce acertain dissolution rate. Further, connecting layer 320 can act as areservoir for drug delivery. A preferred structure for connecting layer320 is tailored to provide the desired dissolution rate and drugdelivery rate.

Referring still to FIG. 3, adhesive layer 310 and barrier layer 330 mayeach be structured as described in reference to FIG. 2. In certainembodiments, when adhesive layer 310 is structured to provideadhesiveness and barrier layer 330 is structured to provide mechanicaldurability, connecting layer 320 can be structured to provide a durablebond between the two layers. That is, the structure of adhesive layer310 may be highly porous, for example, while the structure of barrierlayer 330 may be densely packed, for example. Connecting layer 320 mayprovide a structural gradient between these two different structures toform a durable connection between the layers.

FIG. 3 illustrates a three layer dressing. The dressings of certainembodiments of the present invention may be composed of more than threelayers. The adhesive layer of certain embodiments may be comprised ofseveral layers, each having a structure and composition the same as ordifferent from another layer. Each layer in a set of adhesive layers maybe structured to achieve specific properties. Similarly, the connectinglayer and the barrier layer may each be comprised of several layers,each having a structure and composition the same as or different fromanother layer. In certain embodiments, one or more layers of thedressing may be colored to provide ease of use and/or to identify thedifferent layers. In some embodiments, part or all of the dressing maybe colored to help a physician and/or patient to confirm that thedressing is still in place, how much of the dressing has dissolved orthe like.

In a number of embodiments, one or more layers of a mucosal tissuedressing may be configured to hold and elute one or more therapeutic orother substances. For example, steroids, anesthetics, anti-inflammatorymedications, mucolytics, antibiotics and many other substances may beintroduced into a layer of a mucosal tissue dressing so as to elute outof the dressing at a desired rate once it is applied to tissue. Manydiseases are localized to a specific part of the body and are mosteffectively treated with therapy targeted directly to the disease site.The local delivery provided by a drug eluting mucosal tissue dressingmay allow for higher therapeutic concentrations of drug where it isneeded and may prevent many unwanted systemic side effects.

Diseases along the digestive tract are often difficult to target due toa mucosal surface that does not encourage binding of standard dressingmaterials and a constant flux of digestive juices that work to bothdegrade and wash away mucoadhesive drug delivery products. Variousembodiments of the present invention may involve a mucoadhesive filmthat may include a drug delivery aspect and a barrier layer that allowsfor prolonged drug delivery. Diseases of the digestive tract that maybenefit from this therapeutic drug delivery method include:

Diseases or treatments of the oral cavity such as oral candida infection(thrush), xerostromia (dry mouth), post surgical management of pain andinfection, oral cancer, halitosis, delivery of fluoride, softening ofgums during orthodontic treatment and the like.

Diseases or treatments of the throat such as tonsillitis orpost-surgical management of tonsillectomy or other throat surgicalprocedures, treatment of vocal cord dysfunction such as paralysis orpolyps, laryngeal cancer and the like.

Diseases or treatments of the gastrointestinal tract such as gastriculcers, gastritis, reflux disease, cancer, helicobacter pyloriinfections, proton pump dysfunction, obesity and the like.

In various embodiments, drug may be incorporated into the dressing atthe time of manufacture or at the time of application. The dressing maybe biodegradable or it may be non-degradable and removed as needed. Oneor more drugs may be incorporated into the same film and delivered onthe same or different release schedules. The dressing may be appliedmanually or with the use of endoscopy tools. The dressing may bedesigned to release drug either toward the mucosal surface or into theoral/laryngeal/gastrointestinal tract.

Drug delivery to mucosal surfaces has been hampered by the lack of filmforming agents that can effectively bind that tissue and remain in placefor a sufficient time to deliver therapy for the period needed. A largenumber of oral dressing materials have been developed such as SaliCeptOral Patch by Carrington Laboratories and Gelclair Oral gel by SinclairPharmaceuticals. These materials adhere to oral mucosa but they dissolvein a matter of minutes and so are not useful for prolonged delivery oftherapeutic agents.

In various embodiments, a mucosal dressing of the present invention mayadhere firmly to mucosal surfaces and remain in place for a period ofdays to weeks. In some embodiments, the dressing may be directly placedover the site of a gastrointestinal ulcer or lesion and may provideprolonged continuous drug delivery to that site. In some embodiments,the mucosal dressing may be placed endoscopically into thegastrointestinal tract.

If the dressing material is designed not to degrade, then the drugdelivery system can also be removed and drug delivery terminated ifnecessary. The dressing may include a barrier layer that preventsdissolution of the material by the acidic contents of the digestivetract. Similarly, the barrier layer may prevent the dressing frominteracting with food, essential nutrients or orally administered drugsin the digestive tract.

In some embodiments, a therapeutic substance may be designed to passthrough the blood brain barrier (BBB) to enter the central nervoussystem (CNS). The most important factor limiting the development of newdrugs to treat CNS disease is the BBB that limits penetration of mostCNS drug candidates. One location where the BBB does not function tolimit penetration is at the interface between the nasal epithelium andthe brain. When delivered from the nasal epithelium, CNS drugconcentration may exceed systemic plasma concentrations. Delivery fromthe nose to the CNS also occurs along both the olfactory and trigeminalneural pathways and additionally targets nasal associated lymphatictissues and deep cervical lymph nodes. Thus, delivery of drugs throughthe nasal mucosa may be one way to target the CNS and or lymph nodes.

Some of the CNS diseases that may be addressed using intranasallyadministered drugs eluted from a mucosal tissue dressing of the presentinvention include Alzheimer's disease, Parkinson's disease, braincancer, stroke, migraine, psychoses, epilepsy, meningitis, memory lossor other forms of neurodegeneration, lymphoma, neuroAIDS, variousaddictions, certain forms of obesity and the like. Drug formulations mayinclude, for example, nasal sprays and muco-adhesive microemulsions,some of which may be developed in the future.

A tissue dressing of the present invention, in some embodiments, may beused to provide localized and controlled drug delivery selectively tothe CNS. The drug may be encapsulated into the dressing at the time ofmanufacture or it may be added to the dressing at the time of placementon the nasal or sinus mucosa. Additional drug may be added as needed ata later time in some embodiments of this invention. The dressing may bebioresorbable and eventually degrade so that it does not have to beremoved, or it may be non-absorbable and removed as needed forreplacement or cessation of therapy.

A drug delivered from a mucosal dressing will be delivered much morelocally at the site of placement and can be directed downward into themucosal tissue rather than into the airway. Not all drugs can be easilyformulated so as to be aerosolized and the formulation usually requiresadditional excipients with the potential for adverse effects,particularly on mucosal tissue. Nasal sprays will likely require repeatadministration of relatively high doses so as to achieve a therapeuticdose at the target site and to maintain that dose within the therapeuticrange between administrations. In contrast, a mucosal dressing maydeliver drug at a steady or controlled rate continuously for as long asit is needed. This generally allows for delivery of lower doses and doesnot cause “peak and valley” drug concentration changes over time. Insome embodiments, the drug reservoir may be replenished with drug at alater time if necessary for continued therapy or it may be removed ifthere is a need to quickly halt therapy. Novel drug delivery films arenow under development that allow for delivery of more than one drugsimultaneously but at different rates based on their pharmacokineticprofile.

In some embodiments, a drug delivery dressing may be applied as apreliminary evaluation of drug effectiveness to treat a CNS conditionprior to a more invasive drug delivery technique. In this way differenttherapeutic candidates can be screened for potential effectiveness in anindividual patient before they are subjected to a risky surgicalprocedure.

The preceding discussion highlights certain features, characteristics,and/or properties of mucosal tissue dressings. Many of these featureswill be useful in certain of the specific embodiments described below.

FIG. 4 illustrates an alternative embodiment of a tissue dressing 40having a curved shape to conform to a tonsil bed from which a tonsil hasbeen removed. Dressing 40 has an outer rim 42 configured for placementon normal, non-operated tissue surrounding the tonsil bed and a concavecentral region 44 configured to conform to the tonsil bed. Outer rim 42may be the same thickness as central region 44, or outer rim 42 may bethinner than central region 44. In some embodiments, outer rim 42 isthicker than central region 44. Outer rim 42 can help dressing 40 stayin place by providing increased contact area with healthy tissue.

Still referring to FIG. 4, dressing 40 may have different shapes andsizes that are adapted for use in surgical beds and/or patients ofvarious sizes. Dressing 40 may come in a range of predetermined shapesand sizes. For example, dressing 40 may have a range of sizes of centralregion 44 in which the depth, diameter, and/or radius of curvature mayvary. Similarly, outer rim 42 may have a range of diameters. A physiciancan select an appropriately sized and shaped dressing for placementfollowing surgery. Alternately, a physician can shape dressing 40 tocreate a custom fit to a patient's surgical bed. In another alternateembodiment, a physician can combine an outer rim 42 of specific shapeand size with a central region 44 of specific shape and size to form acustomized dressing.

Referring again to FIG. 4, outer rim 42 and central region 44 may beformed of the same material or of different materials. The materialsand/or texture of outer rim 42 can be chosen to minimize irritation orinjury to the healthy tissue on which it is placed. The materials and/ortexture of central region 44 may be chosen to facilitate healing of thesurgical bed. Central region 44 and/or outer rim 42 can also includetherapeutic or other agents.

FIG. 5 illustrates an alternative embodiment of a tissue dressing 50 inwhich the dressing has a cylindrical shape. Cylindrical dressing 50 canbe used in or near tubular body cavities, such as, for example, aEustachian tube. Fluid in the Eustachian tubes is a common problem, anda dressing having certain characteristics may be useful in Eustachiantube treatment. For example, cylindrical dressing 50 may be placed atthe base of the Eustachian tube and may deliver one or more therapeuticsubstances, such as a steroid or a surfactant. Cylindrical dressing 50can be designed to act as a one-way valve to allow flow out of theEustachian tube but not into it. Cylindrical dressing 50 can be designedto absorb fluid, or may perform some combination of these or otherfunctions. The choice of materials, structure, and texture for the wallsof cylindrical dressing 50 will affect the function and properties ofthe dressing, as is disclosed elsewhere in this document.

FIG. 6 illustrates one embodiment of the present invention in which adressing is customized for application to a surgical bed. Dressing 400has a barrier surface 410 and an optional backing 420. In certainembodiments of the present invention, the dressing may have a backing onits adhesive surface, its barrier surface, or both. In the embodimentillustrated in FIG. 6, backing 420 covers the adhesive surface (notnumbered) of dressing 400. Backing 420 is illustrated as having anoptional tab to facilitate removal. A backing can preserve the integrityof the adhesive surface or the barrier surface prior to use. A backingcan also prevent premature release of any agents from the dressing.

Referring still to FIG. 6, scissors 450 can be used to cut dressing 400into a custom shape to match the surgical bed. Dressing 400 may come inpreshaped configurations, such as a butterfly shape, a lobed shape, atriangular shape, or any other conventional bandage shape. Dressing 400may also have a curved shape or another shape extending out of the planeof the dressing. Additionally, dressing 400 may be moldable such thatwhen manipulated by a user, dressing 400 retains the shape its moldedshape. The materials selected for the adhesive, barrier, and connectinglayer (if present) may provide this moldable property.

In certain embodiments of the present invention, an adherent material isapplied onto post-surgical beds to cover and protection them fromabrasion by food or other items. The sticky material can be a polymer.Application of the material can be by spraying, wiping, painting orother method. The surgical bed is protected from mechanical disruptionor irritation. Additionally, the barrier may protect the surgical bedfrom infiltration by pathogens or other harmful infiltrates. Thedressing may provide a platform useful for drug delivery or the releaseof other therapeutic substances.

FIG. 7 illustrates a tissue dressing 70 and a method for packaging thesame. In this embodiment, tissue dressing 70 includes a tissue adherentlayer 71 which includes one or more apertures 72. Tissue dressing 70 mayalso include an absorbent layer 73 and a barrier layer 74. Adherentlayer 71 has an outer surface capable of adhering to mucosal tissue andan inner surface capable of adhering to absorbent layer 73. Adherentlayer 71 is made from materials suitable for these purposes as describedelsewhere in this application. Absorbent layer 73 is designed to absorbtherapeutic or other agents prior to placement in a surgical bed and toallow those agents to elute out over time. Absorbent layer 73 can have aporous structure (including macroporous, microporous, or nanoporousstructures) to facilitate the uptake and release of agents. Certainmaterials may be preferred over other materials for use with specificagents. For example, a hydrogel material may provide a suitable elutionprofile for a hydrophilic agent, while a more hydrophobic material mayprovide a suitable profile for a hydrophobic agent. Barrier layer 74 canprovide a structural backing for absorbent layer 73, promote resistanceto mechanical abrasion on the outer surface of tissue dressing 70 onceit is applied to the surgical bed, and provide a barrier to elution ofthe agent such that the agent preferentially elutes through adhesivelayer 71 (and/or through apertures 72).

Referring still to FIG. 7, although the entire tissue dressing may bepackaged together, in certain embodiments adherent layer 71 can bepackaged separately from absorbent layer 73 and/or barrier layer 74. Incertain embodiments, and in particular those embodiments in whichadherent layer 71 is packaged separately, a physician may add atherapeutic or other agent to absorbent layer 73 and then apply adherentlayer 71 to absorbent layer 73. Thus, packaging adherent layer 71separately allows for customized agent selection, including customizeddosing. The therapeutic or other substance may be added in any suitableway, such as by injecting with a syringe, pouring out of a container,spraying or the like. In alternative embodiments, all three layers 71,73, 74 may be separate and may be coupled together by the physician orother user. In some embodiments, different absorptive layers 73 may beprepackaged containing different therapeutic or other substances, so thephysician may select an absorptive layer 73 depending on his/her needsfor a particular patient. In alternative embodiments, barrier layer 74may be packaged separately from adherent layer 71 and absorptive layer73.

In some embodiments, whichever layer is applied to the others may act toseal in whatever therapeutic or other substance is introduced intoabsorptive layer 73. This sealing may allow tissue dressing 70 to actlike a fillable reservoir that elutes a substance over time. Asdiscussed above, the layer that is applied to the other layers and thatseals in substance may be tissue adherent layer 71, barrier layer 74, oreven some other layer in alternative embodiments. In some embodiments,the sealing layer may be impermeable, so that loaded therapeutic orother substance(s) must elute through a different layer or through oneor more openings in a layer. Alternatively, the sealing layer may bepermeable or semi-permeable, so that while it seals in the loadedsubstance initially, it allows elution of the substance over time.

FIGS. 8A and 8B illustrate alternative methods of packaging dressingsfor use, according to certain embodiments. Referring to FIG. 8A,multiple tissue dressing may be packaged into a stack 80 joined at astack edge 81. A user can remove one tissue dressing at a time fromstack 80 for use. Similarly, referring to FIG. 8B, multiple tissuedressings may be stored in dispenser 85 and removed through dispenserslot 86.

FIG. 9 illustrates another method of packaging tissue dressings for use,according to certain embodiments. Dispenser 90 includes a roll 91 oftissue dressings which can be removed and cut to an appropriate sizeusing cutting edge 92. A physician can select an appropriate size for atissue dressing from roll 91.

FIG. 10 illustrates one embodiment of the present invention in which thedressing is applied and formed in situ on the surgical bed. Device 500includes reservoir 510, elongate member 520, and distal end 530.Reservoir 510 holds at least one material in a deliverable form, such aliquid or gel. Reservoir 510 may be a syringe barrel or similar device.Reservoir 510 connects to elongate member 520. Elongate member 520 hasat least one lumen through which the material contained in reservoir 510can pass. Elongate member 520 can be flexible, rigid, or a combination.The desired flexibility or rigidity of elongate member 520 depends inpart on the treatment site. For example, a treatment site in a remotebody lumen may require a flexible elongate member capable of providingaccess through tortuous anatomy.

Still referring to FIG. 10, the material from reservoir 510, flowingthrough elongate member 520, is applied to the treatment site throughdistal end 530. Distal end 530 can have a cross sectional dimensionapproximately the same as a cross sectional dimension of the lumen ofelongate member 520. Alternatively, distal end 530 may taper or flare sothat it has different dimensions than the lumen of elongate member 520.Also, distal end 530 can be configured to provide a specific spraypattern. For example, distal end 530 can be configured as an end capwith a pattern of holes. In FIG. 10, spray pattern 550 is used to formlayer 540.

Also, distal end 530 can be malleable, such that a user can pre-shape anangle that distal end 530 forms with elongate member 520 to direct theapplication of material. Distal end 530 can be steerable, providing theuser with the ability to control the direction of spray applicationafter the device has reached the treatment area.

While distal end 530 is capable of applying material in spray pattern550, it can also apply material in any way that a liquid, gel, or othermaterial can be applied. For example, a liquid or a gel may seep, weep,or ooze from distal end 530. Known devices suitable for applyingmaterial include needles, cannulas, and catheters. Other devices capableof painting or wiping material onto a surgical bed, such as a swab, arealso useful.

In one embodiment, a sprayable or flowable tissue dressing material maybe applied areas other than post-tonsillectomy/adenoidectomy surgicalbeds. Dressing materials applied in such other areas can have differentproperties or characteristics than post-tonsillectomy/adenoidectomydressings in order to perform the function required in such other areas.For example, a flowable tissue dressing may be applied before a surgeryon mucosal tissue to reduce bleeding and oozing after the procedure. Inanother embodiment, a sprayable material may be applied inside aparanasal sinus to reduce or stop ciliary movement and thus to keep adrug that has been delivered to the sinus from being moved/flushed outof the sinus by ciliary action. A sprayable or flowable dressing mayalso be used to plug CSF leaks, just as a solid film may also be used.

FIGS. 11A and 11B illustrate another embodiment of the present inventionin which the dressing is applied and formed in situ on the surgical bedusing an energy source. Distal part 600 of the device includes elongatetubular member 620 and elongate conductor 630. Elongate tubular member620 is similar to elongate member 520 in that it can connect to areservoir and can be used to supply and apply material to a treatmentsite. Elongate conductor 630 is shown coupled to elongate tubular member620, although in certain embodiments elongate conductor can be aseparate device. Elongate conductor 630 is capable of conducting energy,such as ultraviolet light, visible light, infrared light, radiofrequencyenergy, sound waves (including ultrasound), heat, other forms of energy,or combinations thereof. Elongate conductor 630 may also be used toprovide a vacuum or promote air flow over the dressing to facilitatedrying, curing, or adhesion of the material. Elongate conductor 630 hasdistal conductive end 650, which can focus or target the energyconducted along elongate conductor 630. Distal conductive end 650 can bea lens, for example. The energy conducted by elongate conductor 630 isuseful for curing the material applied to the treatment site into alayer, such as dressing layer 660.

Referring to FIG. 11B, dressing layer 660 is formed of the liquid, gelor other material applied to the treatment site. In certain embodiments,the applied material can be transformed from one state to another, forexample, from liquid to gel, from liquid to solid, from gel to solid, orany combination thereof. Such transformations can be termed “curing” andinclude those conventionally known as gellation, solidification,polymerization, and processes equivalent to each such transformation.These transformations can be carried out in any of the conventionallyknown ways. For example, a polymerization of a liquid into a gel orsolid at the treatments site may occur when the applied materialcontacts fluid at the treatment site, as can happen withN-vinyl-2-pyrrolidine (NVP). Or, polymerization at the treatment sitecan be carried out by applying both a polymerizable liquid and apolymerizing agent, such as linear polyethylene oxide. Similarly,gellation at the treatment site can be carried out by applying both agellable liquid (or gel) and a gelling agent, such as NVP.

In certain embodiments of the present invention, the dressing cancontain drugs or active substances that can be released into the localtissue environment. Examples of suitable drugs or active substancesinclude anti-inflammatories, antibiotics, analgesics, anesthetics, andcombinations thereof. Specific examples of suitable drugs or activesubstances include eucalyptus, lidocaine, or steroids. Certainembodiments of the present invention can include substances that promotetissue adhesion, such as growth factors or RGD peptides. Such adhesionpromoting substances can be preferentially located in an adhesive layeror on an adhesive surface of the dressing. In other embodiments, atissue dressing may include drug to help prevent post-surgical tissueadhesion. Certain embodiments can include substances that discouragebacterial adhesion or colonization or the accumulation of debris, suchas colloidal silver or microbial toxins. Such adhesion preventingsubstances can be preferentially located in a barrier layer or on abarrier surface. Other embodiments of the present invention can includehemostatic agents such as fibrinogen or thrombin that can aid in thereduction of post-surgical bleeding. In some embodiments, the tissuedressing may include a drug that inhibits cell growth. For example, insome tonsillectomy cases, if a tonsil is not completely removed, thetonsil may grow back over time. If cell growth inhibition drugs arelocally applied, however, such regrowth may be inhibited. If thesurgical procedure involves removal of cancerous tissue, anti-cancertherapies may be included in the dressing.

Any of the substances discussed above, or any combination thereof, canbe included in the preformed dressing embodiments or in the in situformed dressing. In some embodiments, two or more therapeutic substancesmay be contained in and delivered from one tissue dressing. For example,a dressing with multiple layers may contain a different substance ineach layer. Drug delivery mucosal tissue dressings may be placed in anysuitable location in the throat, mouth, nasal cavity, paranasal sinusesor the like to perform a desired function. For example, in oneembodiment, small pieces of tissue dressing containing steroid may beplaced on or in nasal polyps to shrink the polyps. In anotherembodiment, a tissue dressing may be placed in the nasal cavity todeliver drug to the olfactory nerve and from there to the centralnervous system, for example for treating Alzheimer's Disease, meningitisor the like.

Embodiments of the present invention described above may be constructedin a variety of ways. Certain manufacturing methods and materials may besuitable for various embodiments, whether they are preformed dressingsor in situ formed dressings. A description of a certain method ormaterial in reference to a specific dressing embodiment is not meant tolimit that use of that method or material to that specific embodiment.

The material used in certain embodiments can be polymers. Suitablepolymers may include the naturally-occurring and synthetic versions ofthe following: polysaccharides (including, for example, cellulose-basedpolymers, alginate-based polymers, chitin and chitosan based polymers,and glycosoaminoglycan-based polymers), protein polymers (including, forexample, collagen, elastin, laminin, poly(amino acids) andpseudopoly(amino acids)), poly(α-hydroxy esters), polycaprolactones,poly(ortho esters), polyanhydrides, polyhyrdroxybutyrates,polyphosphazenes, polydioxanones, polyoxalates, polyethers (including,for example, polyethylene glycol, polypropylene glycol, polyethyleneoxide, polypropylene oxide), polyimines, polyurethanes, poly(vinylalcohols) and copolymers, blends and composites thereof. More generally,any biomaterial displaying one or more of the properties describedherein as desirable for certain embodiments of the present invention maybe suitable.

Materials may be chosen for use in certain embodiments for their abilityto form a hydrogel. A hydrogel is typically formed from a polymernetwork in which a high volume water in dispersed. The polymer backboneis typically insoluble in water and may have polar groups appended to itto promote interaction with water. Hydrogels generally are flexible andmechanically similar to living tissue, in part due to the high watercontent.

Materials may also be chosen for their ability to degrade or dissolveafter implantation. Many of the polymeric materials listed above areknown to degrade or dissolve in vivo. As described above, the materialsmay surface-erode, bulk-erode, or both. Both chemical composition andthe physical structure of an implanted material can affect thedegradation rate. In various embodiments, surfaces and layers of thedressing will be designed such that degradation or dissolution occursfrom about 48 hours to about 14 days after implantation. In certainembodiments, the adhesive layer degrades faster than the barrier layerwhen in contact with saliva.

Materials which may be used to form the adhesive layer and/or adhesivesurface may include but are not limited to cellulose-based polymersbased on ethyl cellulose, methyl cellulose, carboxymethyl cellulose,hydroxypropyl methyl cellulose or combinations thereof. Other materialsfor use in the adhesive layer or adhesive surface may include but arenot limited to polyvinylpyrrolidone, polypropylene glycol, hyaluronicacid, collagen, chitin, chitosan, glycosaminoglycans, proteoglycans,fibrin, fibrinogen or the like.

Materials which may be used to form the barrier layer or barrier surfacemay include but are not limited to polymers based on ethyl cellulose,methyl cellulose, polyethylene glycol, and polypropylene glycol.

As described above, both the adhesive surface and the barrier surfacecan be treated to provide adhesive or bio-resistive properties. Forexample, biomaterial surfaces can be chemically treated such that smallmolecules, peptides, proteins, or functional groups are bonded to thesurface. Such surfaces can exhibit dramatically improved adhesive orbio-resistive properties. Alternatively, for example, surfaces may betreated by bombarding them with plasma or ions or other energy-drivensurface modification techniques or their equivalents. Such surfaces canalso exhibit dramatically improved adhesive or bio-resistive properties.Moreover, the texture of a surface can also influence its adhesive orresistive properties. Dimples or pores can be molded into a surface,machined into a surface, chemically etched, or ablated with a laser, forexample. Other textures or patterns are also possible

Additionally, the three-dimensional structure of an adhesive layer orthe barrier layer can promote or discourage adhesion, and can promotemechanical strength. Porous layer can be formed using gas-evolutionfoaming techniques, incorporating and subsequently dissolvingporosigens, or by phase-separation techniques. Alternatively, forexample, fibrous surfaces can be produced using techniques common to thetextile industry, such as weaving or felting. The size and shape of thepores and the interstices between fibers can influence the adhesivenessand mechanical properties of a layer.

Both the surface texture and the three-dimensional layer structure ofcertain embodiments can influence the drug delivery profile ofdressings. For example, drugs or active substances that diffuse from thebulk of the layer through the surface can be delivered at a higher ratein a high surface area dressing than in a comparably sized low surfacearea dressing. Similarly, a higher internal porosity for a dressingresults in a higher diffusion rate. Of course, many other parametersinfluence the drug delivery profile of an implant, such as thesolubility of the drug in the polymer carrier and the solubility of thedrug in the biological milieu.

FIG. 12 illustrates one method of use of an embodiment of the presentinvention in which a preshaped dressing is placed on a surgical bed.Patient 700 has a post-operative site 710, in which mucosal tissue hasbeen damaged. After the surgical procedure has concluded, a user canapply preshaped dressing 730 to post-operative site 710 using forceps720. As previously discussed, preshaped dressing 730 may have been cutor shaped by the user to customize it for this particular surgical bed,or it may have been provided in a shape and size already suitable forthis particular surgical bed. In certain embodiments, the dressing maybe applied in a dry state and made moist by the application of saline tothe dressing and/or the surgical bed.

FIG. 13 illustrates one method of use of an embodiment of the presentinvention in which a dressing is formed in situ on a surgical bed.Patient 800 has a post-operative site 810, in which mucosal tissue hasbeen damaged. After the surgical procedure has concluded, a user caninsert the distal section of delivery device 820 such that the distalend of delivery device 820 is near post-operative site 820. Material canbe applied through delivery device 820. The material may form layers asdescribed above. Ultimately, the applied material forms in situ dressing830.

The devices and methods described in the various embodiments above havein some cases made particular reference to mucosal tissue associatedwith surgical procedures on tonsils or adenoids. However, dressingscapable of treating mucosal tissue associated with surgical procedureson the sinus, turbinate, gum, cheek, pharynx, esophagus, stomach, gut,or anus are also contemplated by these descriptions.

In some embodiments, a tissue dressing may be used as a supportstructure or to add mass to a piece of tissue for a particular function.For example, FIG. 14 illustrates the results of a method for repairing anasal septum 1400 using a tissue support 1410. In surgical procedures totreat a deviated septum, a physician typically uses a splint or similardevice to support the repaired septum. In the embodiment illustrated inFIG. 14, tissue support 1410 has been placed within, or at leastpartially within, repaired septum 1400. In contrast to a splint, whichcan be difficult to insert and maneuver and requires eventual removalfrom the healed septum, tissue support 1410 can add structure to therepaired septum by, in part, adhering to the tissue. Tissue support 1410can include therapeutic, analgesic, anesthetic or other agents. Tissuesupport 1410 can be designed to degrade over time thereby eliminatingthe need for later removal.

FIG. 15 illustrates another exemplary embodiment in which a tissuesupport film 1500 is adhered to the back of tongue 1510 to make thatportion of tongue 1510 more rigid. There is some evidence that sleepapnea may be caused by the tongue retracting backwards while sleepingand that a stiffer tissue in the posterior aspect of the tongue mayprevent this retraction. In some embodiments, support film 1500 mayinclude longitudinal slots for facilitating breathing while still makingthe posterior tongue thicker. In an alternative embodiment, a tissuedressing infused with lidocaine or other anesthetic may be applied to asurgical site after a traditional sleep apnea surgical procedure. Aswith other embodiments, the materials, structure, and texture of supportfilm 1500 can be chose to meet the performance goals of theseembodiments.

In other embodiments, a tissue dressing may be used for other purposes.For example, a tissue dressing may be used as a plug, such as to stopCSF leaks after skull base surgery, as mentioned above. A dressing mayalso be used to cover the site of a puncture through the canine fossainto a maxillary sinus. Such punctures are sometimes formed, forexample, to access a maxillary sinus to perform sinus surgery. A tissuedressing may be used in oral surgery or tooth extractions to help stopor minimize bleeding.

In yet another embodiment, a mucosal tissue dressing film may be used asan iontophoresis pad for delivering drug to or through a tissue.Iontophoresis generally involves driving a substance across a tissue byapplying electrical energy to the substance and driving the substancetoward a receiver of the electrical energy. In one embodiment, thetissue film may be used in this capacity for driving substance acrossany tissue membrane in the ear, nose, throat or mouth.

Example 1

In this example, dressings were made from films composed of modifiedcellulose.

Method—all the raw materials are prepared into solutions in certainconcentrations respectively; then the solutions are coated on a PTFEsheet individually or in mixture with single or double layers to makedifferent films.

1. Raw Materials

Polypropylene glycol (PPG), Alfa Aesar Cat# 40811, Lot#K28Q011, used asreceived.

DI water was prepared on site by DI water generation system.

The following raw materials are prepared into solutions for use:

Ethanol, Aldrich Cat# 493546-1 L, Lot# 06862EH

Ethyl cellulose (EC), Spectrum Cat# ET110, Lot# UT0371

Methyl cellulose (MC), Aldrich Cat# M0555-100G, Lot# 037K00611

Hydroxypropyl methyl cellulose (HPMC), Aldrich Cat# H3785-100G, Lot#086K0115.

2. Solution Preparation

Ethyl Cellulose Solution Preparation

Composition: 20 wt % ethyl cellulose (EC) in USP grade ethanol.

Example: 37.5 g EC in 150 g Ethanol.

Preparation: weigh desired amounts of EC and ethanol, mix them togetherin a storage bottle, stir the solution on vortex mixer, and leave it for2-3 days before use.

Methyl Cellulose Solution Preparation

Composition: 5 wt % methyl cellulose (MC) in USP ethanol/DI water (1/1wt).

Example: 32 g MC in 300 g ethanol/300 g DI water.

Preparation: weigh desired amounts of MC, ethanol, and DI water, mixthem together in a storage bottle, then add DI water, stir the solutionon vortex mixer, and leave it for 2-3 days before use.

Hydroxypropyl Methyl Cellulose Solution Preparation

Composition: 7 wt % hydroxypropyl methyl cellulose (HPMC) in USPethanol/DI water (1/1 wt).

Example: 28.6 g HPMC in 190 g ethanol/190 g DI water.

Preparation: weigh desired amounts of HPMC, ethanol, and DI water;transfer weighed HPMC into a storage bottle, transfer ethanol into thebottle and mix the solution to let the HPMC powder uniformly disperse inethanol; add weighed DI water into the bottle while stirring untilfinish; stir the solution, and leave it for 2-3 days before use.

3. Equipment or Tools

Vacuum oven: Lab-Line Instruments, model# 3608, used for film drying

Gel dryer: Bio-Rad, model# 583, used for film drying and flattening

Shaker: New Brunswick Scientific, model# Classic Cl, used for solutionstirring

PTFE sheet: 11.0 mm thick, in sizes: 6×6, 6×12, 6×18 cm², used as a filmcoating substrate

PTFE coated tray: bottom size: 10×20 cm², used as a film coatingsubstrate

Stainless steel spatulas: used for film coating 500 ml wide mouthreagent bottles: used for solution storage

Glass beakers: 250 ml, used for solution mixing for film coating

Disposable pipettes: used to transfer PPG liquid

Aluminum foil: used cover the coated films.

4. Film Preparation

The thickness of the prepared film primarily depends on several factors,e.g., material bulk density, substrate surface area, quantity ofmaterial solution coated on the substrate surface. The following formulacan be used to estimate the thickness of the prepared dry film:

q=(W×C)/(D×A)

where, W is the quantity of material solution used for casting a film; Crefers to the solid content of the material solution in weight percent;D is material bulk density; and A stands for the area of the substratesurface. PTFE and PE polymer sheets or dishes, or PTFE coated tray, canbe used as substrate surfaces for film casting.

1) Single-Layer Film Preparation

General procedures:

a) Based on the above formula, a determined quantity of materialsolution (or solutions, if a solution mixture is used) is weighed (orthen mixed).

b) Coat the weighed solution (or mixed solutions) on the surface of agiven substrate sheet or dish.

c) Put the coated substrate sheet or dish in chemical hood or vacuumoven to dry slowly.

d) After the film is fully dried, peel it off from the substratesurface, weigh it and measure its thickness.

Example of Single-Layer Film:

HPMC single-layer film preparation on a 6×18 cm2 PTFE sheet.

Targeted thickness: 0.3 mm, dry film density: 0.85 g/cm³

Weighing the PTFE sheet (24.16 g), and weighing 39.36 g 7 wt % HPMCsolution on the PTFE sheet, uniformly flattening the viscous HPMCsolution on the whole sheet, putting it in a tray with foil cover, andthen place the tray in vacuum oven to dry slowly (about 65 hrs).

Weigh and measure the thickness of the dried film.

2) Double-Layer Film Preparation

General procedures:

a) The protective layer is coated first according to the procedures of1a, 1b, and 1c.

b) After the protective layer is partially dried (Dry for 1˜2 hoursdepending on the expected film thickness. The extent of dryness can beobserved as loss of the wet area of the coated surface). Start to coatthe top layer.

c) The top layer is coated according to the procedures of 1a, 1b, and1c.

d) After the double-layer film is fully dried, peel it off from thesubstrate surface, weigh it and measure its thickness.

Example of Double Layer Film

HPMC double-layer film preparation on a 6×18 cm2 PTFE sheet.

Film structure: EC:MC:PPG/HPMC:PPG=4:4:2/8:2 (wt)

a) Protective Layer

Targeted thickness: 0.1 mm, dry layer density: 0.67 g/cm³,

Weigh the PTFE sheet (24.58 g).

Weigh and zero the empty beaker. Weigh 1.86 g 20 wt % EC solution, 7.5 g5 wt % MC solution, and 0.186 g PPG in the beaker, mixing the solutionsinto a uniform slurry (7.11 g of this mixture will be used to coat alayer on 6×18 cm2 PTFE sheet, assuming no solvent evaporation). Weighthe mixture again to calculate the solvent weight loss, then transferthe mixture in an equivalent weight to the theoretical amount of 7.1 μgto the PTFE sheet. Uniformly flatten the mixture on the whole sheet, andthen put it in chemical hood for solvent evaporation.

b) Adhesive Layer

Targeted thickness: 0.2 mm, dry layer density: 0.85 g/cm³.

Weigh the protective layer coated sheet and monitor the remaining weightwith the time.

Weigh and zero the empty beaker. Weigh 30 g 7 wt % HPMC solution, and0.502 g PPG in the beaker, mixing the solutions into a uniform slurry(20.92 g of this mixture will be used to coat a layer on the abovecoated protective layer, assuming no solvent evaporation); when theremaining weight percentage of the coated protective layer is around 25wt %, weigh the mixture again to calculate the solvent weight loss, thentransfer the mixture in an equivalent weight to the theoretical amountof 20.92 g onto the protective layer. Uniformly flatten the mixture onthe whole layer, and then put it in hood, vacuum oven, and gel dryer,for to dry slowly, e.g, Hood—30 min, 50° C. oven—3 hr, 35° C. oven—17hr, 50° oven—4 hr, 70° C. gel dryer—2 hr.

Weigh and measure the thickness of the dried film. e.g., 2.5 g and 0.31mm for film CMT1114-1a.

Example of Multilayer Film

MC double-layer film preparation on a 6×18 cm² PTFE sheet.

Film structure: EC:MC:PPG/MC:PPG=4:4:2/8:2 (wt)

a) Protective Layer

Targeted thickness: 0.1 mm, dry layer density: 0.67 g/cm³,

Weigh PTFE sheet (24.62 g).

Weigh and zero the empty beaker Weigh 1.86 g 20 wt % EC solution, 7.5 g5 wt % MC solution, and 0.186 g PPG in the beaker, mixing the solutionsinto a uniform slurry (7.12 g of this mixture will be used to coat alayer on 6×18 cm2 PTFE sheet, assuming no solvent evaporation); Weighthe mixture again to calculate the solvent weight loss, then transferthe mixture in an equivalent weight to the theoretical amount of 7.11 gto the PTFE sheet. Uniformly flatten the mixture on the whole sheet, andthen put it in chemical hood for solvent evaporation.

b) Adhesive Layer

Targeted thickness: 0.2 mm, dry layer density: 0.85 g/cm³.

Weigh the protective layer coated sheet and monitor the remaining weightwith the time.

Weigh and zero the empty beaker. Weigh 40 g 5 wt % MC solution, and 0.5g PPG in the beaker, mixing the solutions into a uniform slurry (29.39 gof this mixture will be used to coat a layer on the above coatedprotective layer, assuming no solvent evaporation); when the remainingweight percentage of the coated protective layer is around 25 wt %,weigh the mixture again to calculate the solvent weight loss, thentransfer the mixture in an equivalent weight to the theoretical amountof 29.39 g onto the protective layer. Uniformly flatten the mixture onthe whole layer, and then put it in hood, vacuum oven, and gel dryer,for to dry slowly, e.g, 35° C. oven—15 hr, 50° C. oven—8 hr, 35° C.oven—15 hr, 70° C. gel dryer—2 hr.

Weigh and measure the thickness of the dried film, e.g., 2.22 g and 0.29mm for film CMT1114-4.

5. Film Compositions

Adhesive Layer Adhesive Layer HPMC MC Protective Layer Wt of Wt of Wt ofWt of Wt of Wt of Wt of HPMC PPG MC PPG EC MC PPG (g) (g) (g) (g) (g)(g) (g) HPMC Single- 2.76 N/A N/A N/A N/A N/A N/A Layer Film 6 × 18 cm²HPMC Double- 1.41 0.36 N/A N/A 0.28 0.28 0.14 Layer Film 6 × 18 cm² MCDouble- N/A N/A 1.45 0.36 0.28 0.28 0.14 Layer Film 6 × 18 cm²

6. Discussions

1) Solution Preparation

In preparation of material solutions, the solutions should be shelvedfor several days to ensure the solutions become homogenous. If thesolutions are not homogeneous, the films made from the solutions will beuneven.

2) Solution Storage and Use

The prepared solutions should be weighed and then well sealed to preventsolvent evaporation. Solvent loss via evaporation can be calculated byweighing the solutions after and before use. If any solvent loss occurs,the solvent should be added to the recipe amount. Solvent loss willcause the solution concentration to change making it difficult tocontrol the film thickness.

3) Protective Layer Drying

Protective layer drying is critical to the adhesive layer coating. Ifthe adhesive layer is coated onto a protective layer that has not driedsufficiently, the two layers may be mixed together, thus thedouble-layer structure may be destroyed. If the adhesive layer is coatedonto a protective layer that is dried too completely, the two layers maybe easily separated following application.

A factor can be used to estimate the drying extent, that is, theremaining weight percentage of the coated protective layer, which can becalculated by using the following equation:

Remaining weight %=(Wt−Ws)/(Wi−Ws)×100%

where, Wt is the weight of the coated PTFE sheet after drying for acertain time, Ws is the weight of the uncoated PTFE sheet, and Wi is theinitial weight of the coated PTFE sheet. When the remaining weight %falls in the range of 15-30% or the best level of 25%, the adhesivelayer should be coated onto the protective layer immediately.

4) Adhesive Layer Drying

Several problems may be encountered during the drying course of theadhesive layer (including single layer film), especially when producinga thick layer. Generally, cracks, shrinkage, waves, wrinkles, bubbles,and uneven thickness, might be seen if the drying conditions are notcarefully controlled.

Basically, a slow drying process and particularly a slow solventevaporation on the film surface may significantly avoid theaforementioned problems and improve the film drying quality. Meanwhile,wavy shape can be eliminated by using a gel dryer when the film isnearly fully dried.

Example 2 Film Adhesion Strength Test

For the evaluation of the adhesion strength of oral wound dressing filmsamples, An apparatus was set up, which can be used to evaluate the filmsamples for their adhesion performances. Two types of adhesion strength,i.e., lift-off strength and peel-off strength, can be measured throughthe use of the apparatus.

1. Lift-Off Adhesion Strength Test Setup and Procedures

By measuring the vertical detaching force and time, the lift-offadhesion strength of the film adhering to fresh pork steak can betested. The test apparatus 1600 is set up as shown in FIG. 16. Tests areperformed at room temperature, 23 deg. C. The procedures are describedbelow:

1) Cut a sample film 1610 in a certain size, e.g., 15×15 mm²;

2) Use superglue to fix a fresh, boneless pork steak 1620 to the bottomof a dish;

3) Use Scotch tape to fix the string at the center of sample (forsingle-layer film) or sample protective layer (for double-layer film); asmall amount of super glue can be used to further secure the tape to thesample as long as no super glue penetrates the sample to affect itsadhesive properties.

4) Put the sample adhesive layer on the fresh pork steak 1620 surface,and press the film to let it adhere to the steak surface and leave itfor 5 minutes (curing time);

6) After 5 minutes start the timer and immediately add water into theloading cup 1630 drop-by-drop smoothly until either the film is liftedoff or the cup is filled fully;

7) note the time when the film has lifted off the steak.

8) If the film is lifted off, weigh the weight of the loading cup 1630with water and note the weight as the lift-off adhesion strength of thesample.

9) If the loading cup 1630 is added to full level and the film stilladheres to the steak, then record the lift-off time. So the lift-offadhesion strength should be noted as the adhering time under the fullloading.

2. Peel-Off Adhesion Strength Test Setup and Procedures

By measuring the angle (45 degree) detaching force and time, thepeel-off adhesion strength of the film adhering to fresh pork steak canbe tested. The test apparatus 1700 is set up as shown in FIG. 17. Testsare performed at room temperature, 23 deg. C. The procedures aredescribed below:

1) Cut a sample film 1710 in a certain size, e.g., 15×15 mm²;

2) Use superglue to fix a fresh pork steak 1720 on the bottom of a dish;

3) Use Scotch tape to fix the string at the edge of sample (forsingle-layer film) or sample protective layer (for double-layer film); asmall amount of super glue can be used to further secure the tape to thesample as long as no super glue penetrates the sample to affect itsadhesive properties.

4) Put the sample adhesive layer on the fresh pork steak 1720 surface,and press the film to let it adhere to the steak surface and leave itfor 5 minutes (curing time);

6) After 5 minutes start the timer and immediately add water into theloading cup 1730 drop-by-drop smoothly until either the film is peeledoff or the cup is filled fully;

7) Stop the timer and note the time when the film is peeled off.

8) After the film is peeled off, weigh the weight of the loading cup1730 with water and note the weight as the peel-off adhesion strength ofthe sample.

9) If the loading cup 1730 is added to full level and the film stilladheres to the steak, then record the peel-off time. So the peel-offadhesion strength should be noted as the adhering time under the fullloading.

Example 3

In this example, films were tested for properties desirable in adressing. The set time, or the time it takes for a hydrogel to form, wasmeasured for each of the adhesion films. Carboxymethyl celluloseperformed better than hydroxypropyl methyl cellulose, which in turnperformed better than methyl cellulose. All adhesion films and thebarrier film displayed good flexibility and lack of swelling. Alladhesion films and the barrier film remained intact in artificialsaliva. In degradation testing, after 5 days the carboxymethyl cellulosefilm was 70% degraded, the hydroxypropyl methyl cellulose film was 40%degraded, the methyl cellulose film was 25% degraded, and the barrierfilms was 15% degraded. All degradation values are given by weight.

While the invention has been described with reference to certainembodiments, it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted withoutdeparting from the scope of the invention. In addition, manymodifications may be made to adapt a particular situation or material tothe teachings of the invention without departing from its scope.Therefore, it is intended that the invention not be limited to theparticular embodiment disclosed, but that the invention will include allembodiments falling within the scope of the appended claims.

1. A method of assembling an apparatus for post-surgical protection ofmucosal tissue comprising: providing a barrier material and an adhesivematerial; and applying the barrier material to the adhesive material,wherein the barrier material and the adhesive material are adapted toremain substantially intact for a period of time from about 48 hours toabout 14 days after the apparatus is placed proximate to mucosal tissue.2. The method of claim 1 wherein the barrier material is provided in gelform.
 3. The method of claim 1 wherein the barrier material is providedin film form.
 4. The method of claim 1 wherein the adhesive material isprovided in gel form.
 5. The method of claim 1 wherein the adhesivematerial is provided in film form.
 6. The method of claim 1 furthercomprising the step of curing the barrier material, adhesive material,or both.
 7. The method of claim 6 wherein the curing occurs via theapplication of energy.
 8. The method of claim 7 wherein the energycomprises ultraviolet light, visible light, infrared light,radiofrequency energy, ultrasound, heat or combinations thereof.
 9. Themethod of claim 6 wherein the curing occurs via the application of acuring agent.
 10. The method of claim 9 wherein the curing agent iswater.
 11. The method of claim 1 wherein the barrier material, adhesivematerial, curing agent, or a combination thereof is applied via asurgical device.
 12. The method of claim 11 wherein the surgical devicecomprises a swab, needle, cannula, or catheter.
 13. The method of claim11 wherein the barrier material, adhesive material, or both is apreformed film.
 14. The method of claim 13 wherein the preformed film isshaped prior to placement of the apparatus.
 15. The method of claim 14wherein the shaping comprises cutting.
 16. The method of claim 13wherein the barrier material forms a layer substantially covering atleast one side of the adhesive layer.
 17. The method of claim 1 whereinthe adhesive material forms a layer adapted to adhere to mucosal tissue.18. The method of claim 1 further comprising applying a therapeuticagent to the barrier material or the adhesive material.
 19. The methodof claim 18 wherein the therapeutic agent comprises ananti-inflammatory, anesthetic, antibiotic, analgesic, hemostatic, orcombinations thereof.
 20. The method of claim 19 wherein the apparatusis adapted to protect mucosal membranes associated with an adenoid,tonsil, sinus, turbinate, gum, cheek, pharynx, esophagus, stomach, gut,or anus.
 21. A preformed film for post-surgical protection of mucosaltissue comprising: a barrier material; and an adhesive materialcontacting the barrier material, wherein the barrier material and theadhesive material remain substantially intact for a period of time fromabout 48 hours to about 14 days after applying the apparatus to mucosaltissue.
 22. The preformed film of claim 21 wherein the barrier material,adhesive material, or both comprise a polymer.
 23. The preformed film ofclaim 21 wherein the barrier material, adhesive material, or bothcomprise a hydrogel.
 24. The preformed film of claim 21 wherein thebarrier material, adhesive material, or both comprise a polysaccharide.25. The preformed film of claim 21 wherein the barrier material,adhesive material, or both comprise a cellulose, modified cellulose, orcombinations thereof.
 26. The preformed film of claim 21 wherein thebarrier material, adhesive material, or both comprise a ethyl cellulose,methyl cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose or combinations thereof.
 27. The preformed film of claim 22wherein the barrier material, adhesive material, or both furthercomprise a glycolic polymer.
 28. The preformed film of claim 22 whereinthe barrier material, adhesive material, or both further comprisepolypropylene glycol, polyethylene glycol, or both.
 29. The preformedfilm of claim 22 further comprising a therapeutic agent.
 30. Thepreformed film of claim 29 wherein the therapeutic agent comprises ananti-inflammatory, anesthetic, antibiotic, analgesic, or combinationsthereof.
 31. A method of reducing pain after surgical proceduresproximate to a mucous membrane comprising; providing a multilayerdressing, wherein at least one layer is adapted to adhere to tissue andat least one other layer is adapted to provide abrasion resistance; andapplying the multilayer dressing to the mucous membrane, wherein themultilayer dressing remains substantially intact for a period of timefrom about 48 hours to about 14 days after applying the multilayerdressing to mucosal tissue.
 32. The method of claim 31 wherein the atleast one layer adapted to adhere to tissue comprises carboxymethylcellulose, methyl cellulose, and hydroxypropyl methyl cellulose.
 33. Themethod of claim 31 wherein the at least one other layer adapted toprovide abrasion resistance comprises ethyl cellulose, methyl cellulose,and polypropylene glycol.
 34. The method of claim 31 further comprisingproviding a therapeutic agent, wherein the therapeutic agent elutes fromthe multilayer dressing.
 35. The method of claim 31 further comprisingshaping the multilayer dressing.
 36. A multilayer dressing for reducingpain after surgical procedures proximate to a mucous membranecomprising: a tissue adhesive layer adapted to contact the mucousmembrane; and an abrasion-resistant layer substantially covering atleast one side of the tissue adhesive layer, wherein the multilayerdressing remains substantially intact for a period of time from about 48hours to about 14 days after applying the apparatus to mucosal tissue.37. The multilayer dressing of claim 36 wherein the tissue adhesivelayer comprises carboxymethyl cellulose, methyl cellulose, andhydroxypropyl methyl cellulose.
 38. The multilayer dressing of claim 36wherein the abrasion-resistant layer comprises ethyl cellulose, methylcellulose, and polypropylene glycol.
 39. The multilayer dressing ofclaim 36 further comprising a therapeutic agent.
 40. The multilayerdressing of claim 36 wherein the total thickness of the dressing is in arange from about 0.1 mm to about 0.7 mm.
 41. The multilayer dressing ofclaim 36 wherein the total thickness of the dressing is about 0.3 mm.42. The multilayer dressing of claim 36 wherein the thickness of thetissue adhesive layer is about 0.1 mm.
 43. The multilayer dressing ofclaim 36 wherein the thickness of the abrasion-resistant layer is about0.2 mm.
 44. The multilayer dressing of claim 36 wherein the tissueadhesive layer degrades in saliva faster than the abrasion-resistantlayer degrades in saliva.
 45. The multilayer dressing of claim 36wherein the abrasion-resistant layer provides shock absorbingproperties.
 46. The multilayer dressing of claim 36 wherein one or moreof the layers is colored.
 47. The multilayer dressing of claim 36wherein the edges of the dressing are thinner than the center portion ofthe dressing.
 48. A method of reducing abrasion of a tonsil removal siteafter a tonsillectomy procedure, the method comprising applying adressing over the tonsil removal site, wherein one side of the dressingis adapted to adhere to mucosal tissue and an opposite side of thedressing is adapted to provide abrasion resistance.
 49. A method as inclaim 48, wherein at least a portion of the dressing is configured todissolve over time.
 50. A method as in claim 48, further comprisingreleasing a drug from the dressing to reduce pain or promote healing.51. A method as in claim 48, further comprising adding a drug to thedressing before or after applying the dressing over the tonsil removalsite, wherein the drug is released from the dressing over time to reducepain or promote healing.
 52. A method as in claim 48 wherein thedressing is applied in a dry state and saline in applied to keep thedressing moist.